All-cause mortality and survival in adults with 22q11.2 deletion syndrome

Abstract

PurposeGiven limited data available on long-term outcomes in 22q11.2 deletion syndrome (22q11.2DS), we investigated mortality risk in adults with this microdeletion syndrome.MethodsWe studied 309 well-characterized adults (age ≥17 years) with 22q11.2DS and their 1014 unaffected parents and siblings, using a prospective case–control design. We used Cox proportional hazards regression modeling and Kaplan–Meier curves to investigate effects of the 22q11.2 deletion and its associated features on all-cause mortality and survival.ResultsThe 22q11.2 deletion (hazard ratio [HR] 8.86, 95% CI 2.87–27.37) and major congenital heart disease (CHD; HR 5.03, 95% CI 2.27–11.17), but not intellectual disability or psychotic illness, were significant independent predictors of mortality for adults with 22q11.2DS compared with their siblings. Amongst those with 22q11.2DS, there were 31 deaths that occurred at a median age of 46.4 (range 18.1–68.6) years; a substantial minority had outlived both parents. Probability of survival to age 45 years was approximately 72% for those with major CHD, and 95% for those with no major CHD (p < 0.0001).ConclusionFor adults with 22q11.2DS, the 22q11.2 deletion and more severe forms of CHD both contribute to a lower life expectancy than family-based expectations. The results have implications for genetic counseling and anticipatory care.

DGCR8 microprocessor defect characterizes familial multinodular goiter with schwannomatosis

“…Although a clinical diagnosis of autism spectrum disorder was reported in individual III-1 (Figure 1), it is not clear that the characteristics and phenotypes observed in family members are related to the variant (detailed in the Supplemental Text). A causal relation between 22q11-related syndromes and cancer development has not been established, but some instances of tumor development have been reported in 22q11 syndrome patients (27)(28)(29). Neither goiter nor schwannomas have been reported to occur in this syndrome.…”

The role of 22q11.2 deletion syndrome in the relationship between congenital heart disease and scoliosis

“…To determine the scoliosis prevalence in the adult (≥17 years) CHD population, patients were included from an existing sample followed at a specialized adult CHD hospital [18][19][20][21]. All data in this study are part of ongoing studies approved by the local Research Ethics Board.…”

“…1 shows the sample derivation and individuals included and excluded from the present study. We used data available from an existing database for a well-characterized sample of adults with CHD, including CHD type (mostly tetralogy of Fallot) [20], cardiac surgical history, laterality of aortic arch, and presence of musculoskeletal anomalies [18][19][20][21]. CHD complexity was classified as simple, moderate, and severe, following the 2018 guidelines from the American Heart Association and American College of Cardiology [22].…”

“…CHD complexity was classified as simple, moderate, and severe, following the 2018 guidelines from the American Heart Association and American College of Cardiology [22]. We confined the sample to adults with CHD and sufficient molecular genetic data (mostly standard clinical genetic testing and/or research-based genome-wide microarray) [18][19][20][21], to determine presence or absence of a 22q11.2 deletion [17,18]. We used these molecular data to determine individuals confirmed to have the typical chromosome 22q11.2 deletion, that is, at least including the low copy repeat region (LCR)22A-LCR22B and most commonly involving the 2.5 megabase LCR22A-LCR22D region [17,18], (the 22q11.2DS group), and a comparison group comprising those confirmed to have no typical 22q11.2 deletion (the no 22q11.2DS group).…”

“…Exclusion criteria were absence of a chest radiograph obtained between 17 and 40 years of age, presence of an atypical nested (eg, LCR22B-LCR22D, LCR22C-LCR22D) chromosome 22q11.2 deletion [17,18], congenital spinal anomalies or variants (eg, hemivertebra, butterfly vertebrae, and Klippel-Feil), or a documented genetic or other syndromic disorder other than 22q11.2DS (eg, VACTERL, CHARGE, Klinefelter, Goldenhar, Pallister Killian, hemihypertrophy, or fetal ethanol syndromes) ( Fig. 1).…”